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Crossover Study to Compare PK of Once Daily LCP-Tacro Tablets to Generic Tacrolimus Capsules Twice Daily.

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ClinicalTrials.gov Identifier: NCT01962922
Recruitment Status : Completed
First Posted : October 14, 2013
Results First Posted : August 15, 2016
Last Update Posted : June 6, 2018
Sponsor:
Information provided by (Responsible Party):
Veloxis Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Renal Failure
Interventions Drug: LCP-Tacro
Drug: Tacrolimus -IR
Enrollment 50
Recruitment Details 25 November 2013 (first patient enrolled) to 09-Mar-2015 (last patient completed initial pharmacokinetics [PK] portion of the study, the 'PK Cross-over' period), approximately 16 months enrolled from 3 US medical centers:University of Pennsylvania;University of Illinois at Chicago;Washington School of Medicine
Pre-assignment Details  
Arm/Group Title Sequence 1 Sequence 2
Hide Arm/Group Description

•Sequence I: (n=27) Patients will continue on twice-daily IR-Tac capsules on Days 1-7 (24-hour PK profile on Day 7), then patients are switched to Envarsus XR tablets (at a dose 15% lower than their Tac - IR doses) on Day 8. PK on day 14 and 21.

Patients in sequence 1 are on Envarsus XR at Day 21. Patient may continue on extension up to a total of 6 months.

• Sequence II: (n=23) 1 Patients receive Envarsus XR tablets (at 15% lower dose than their IR-Tac dose) on Days 1-7 (24-hour PK profile on Day 7), then patients are switched back to twice-daily Tac - IR treatment beginning on Day 8. PK on days 14 and 21.

Patients in sequence 2 are on Tac - IR at Day 21. Patient have option of continuing in extension portion of the study on Tac - IR for up to 6 months.

Period Title: PK Portion Day 7
Started 27 23
Completed 23 23
Not Completed 4 0
Reason Not Completed
Withdrawal by Subject             3             0
non-compliance             1             0
Period Title: PK Portion Day 14
Started 23 23
Completed 23 23
Not Completed 0 0
Period Title: PK Portion Day 21
Started 23 23
Completed 23 23
Not Completed 0 0
Period Title: Extendion Portion (up to Month 6)
Started 23 23
Completed 18 20
Not Completed 5 3
Reason Not Completed
no longer wished to participate in study             4             3
Physician Decision             1             0
Arm/Group Title Sequence I Sequence II Total
Hide Arm/Group Description Sequence I IR-Tac→Envarsus XR (N = 27) Sequence II Envarsus XR→IR-Tac (N = 23) Total of all reporting groups
Overall Number of Baseline Participants 27 23 50
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 23 participants 50 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
26
  96.3%
20
  87.0%
46
  92.0%
>=65 years
1
   3.7%
3
  13.0%
4
   8.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 23 participants 50 participants
Female
12
  44.4%
9
  39.1%
21
  42.0%
Male
15
  55.6%
14
  60.9%
29
  58.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 27 participants 23 participants 50 participants
27 23 50
1.Primary Outcome
Title Evaluation of AUC(0-24) for Envarsus XR and IR-Tac
Hide Description

Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate AUC(0-24). Arithmetic mean and standard deviation is given below.

Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours.

Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
For this outcome measure the PK population N=46 was used.
Arm/Group Title Envarsus XR Tacrolimus - IR
Hide Arm/Group Description:
Tacrolimus tablets once daily.
Tacrolimus capsules twice daily.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
251.9  (77.78) 247.9  (102.33)
2.Primary Outcome
Title Evaluation of C(Max) for Envarsus XR and IR-Tac
Hide Description

Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate C(max). Arithmetic mean and standard deviation is given below.

Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours.

Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
For this outcome measuure the Protocol PK population of N = 46 was used.
Arm/Group Title Envarsus XR Tacrolimus - IR
Hide Arm/Group Description:
Tacrolimus tablets once daily.
Tacrolimus capsules twice daily.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: ng/mL
16.53  (5.464) 26.84  (13.296)
3.Primary Outcome
Title Evaluation of C(Min) for Envarsus XR and IR-Tac
Hide Description

Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate AUC(0-24). Arithmetic mean and standard deviation is given below.

Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours.

Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
For this outcome measure the Protocol PK population N= 46 was used.
Arm/Group Title Envarsus XR Tacrolimus - IR
Hide Arm/Group Description:
Tacrolimus tablets once daily.
Tacrolimus capsules twice daily.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: ng/mL
7.51  (2.487) 7.06  (2.843)
4.Primary Outcome
Title Evaluation of AUC(0-24) for Envarsus XR and IR-Tac
Hide Description

Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate AUC(0-24). Arithmetic mean and standard deviation is given below.

Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours.

Time Frame Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
For this outcome measure the PK population N=46 was used
Arm/Group Title Envarsus XR Tacrolimus - IR
Hide Arm/Group Description:
Tacrolimus tablets once daily.
Tacrolimus capsules twice daily.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
293.3  (124.40) 225.7  (56.27)
5.Primary Outcome
Title Evaluation of C(Max) for Envarsus XR and IR-Tac
Hide Description

Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate C(max). Arithmetic mean and standard deviation is given below.

Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours.

Time Frame Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
For this outcome measuure the Protocol PK population of N = 46 was used.
Arm/Group Title Envarsus XR Tacrolimus - IR
Hide Arm/Group Description:
Tacrolimus tablets once daily.
Tacrolimus capsules twice daily.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: ng/mL
20.83  (9.265) 26.31  (13.296)
6.Primary Outcome
Title Evaluation of C(Min) for Envarsus XR and IR-Tac
Hide Description

Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate AUC(0-24). Arithmetic mean and standard deviation is given below.

Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours

Time Frame Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
For this outcome measuure the Protocol PK population N= 46 was used.
Arm/Group Title Envarsus XR Tacrolimus - IR
Hide Arm/Group Description:
Tacrolimus tablets once daily.
Tacrolimus capsules twice daily.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: ng/mL
8.34  (3.769) 6.46  (1.692)
7.Primary Outcome
Title Evaluation of AUC(0-24) for Envarsus XR and IR-Tac
Hide Description

Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate AUC(0-24). Arithmetic mean and standard deviation is given below.

Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours.

Time Frame Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
For this outcome measure the PK population N=46 was used.
Arm/Group Title Envarsus XR Tacrolimus - IR
Hide Arm/Group Description:
Tacrolimus tablets once daily.
Tacrolimus capsules twice daily.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
289.3  (111.79) 230.3  (53.83)
8.Primary Outcome
Title Evaluation of C(Max) for Envarsus XR and IR-Tac
Hide Description

Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate C(max). Arithmetic mean and standard deviation is given below.

Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours.

Time Frame Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
For this outcome measuure the Protocol PK population of N = 46 was used.
Arm/Group Title Envarsus XR Tacrolimus - IR
Hide Arm/Group Description:
Tacrolimus tablets once daily.
Tacrolimus capsules twice daily.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: ng/mL
19.71  (8.387) 26.31  (7.871)
9.Primary Outcome
Title Evaluation of C(Min) for Envarsus XR and IR-Tac
Hide Description

Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate AUC(0-24). Arithmetic mean and standard deviation is given below.

Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours.

Time Frame Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
For this outcome measure the Protocol PK population N= 46 was used.
Arm/Group Title Envarsus XR Tacrolimus - IR
Hide Arm/Group Description:
Tacrolimus tablets once daily.
Tacrolimus capsules twice daily.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: ng/mL
8.01  (3.281) 6.62  (1.692)
Time Frame Adverse events were collected from start of first dose of study medication, through and including last dose of study medication during the up to 6 month extension period.
Adverse Event Reporting Description Adverse events are associated with the treatment the patient is on at the onset date of the adverse event and not the portion of the study (e.g. PK or extention portion). The below figures are cumulative for the entire study participation start of study through 6 month extension.
 
Arm/Group Title Envarsus XR Tacrolimus - IR
Hide Arm/Group Description Tacrolimus extended release brand IR tacrolimus
All-Cause Mortality
Envarsus XR Tacrolimus - IR
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Envarsus XR Tacrolimus - IR
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/50 (6.00%)      4/50 (8.00%)    
Cardiac disorders     
Cardiac failure acute  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Infections and infestations     
Cellulitis  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Corona virus infection  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Gastroenteritis viral  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Otitis Media  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Pneumonia  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Metabolism and nutrition disorders     
Hyperglycemia  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Renal and urinary disorders     
Acute renal failure  1  1/50 (2.00%)  1 1/50 (2.00%)  1
Respiratory, thoracic and mediastinal disorders     
Hypoxia  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Envarsus XR Tacrolimus - IR
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/50 (46.00%)      22/50 (44.00%)    
Gastrointestinal disorders     
Constipation  1  0/50 (0.00%)  0 3/50 (6.00%)  3
Diarrhoea  1  3/50 (6.00%)  3 3/50 (6.00%)  3
Nausea  1  3/50 (6.00%)  3 3/50 (6.00%)  3
Infections and infestations     
Nasopharyngitis  1  3/50 (6.00%)  3 5/50 (10.00%)  5
Investigations     
Blood creatinine increased  1  7/50 (14.00%)  8 4/50 (8.00%)  4
Glomerular filtration rate decreased  1  5/50 (10.00%)  5 1/50 (2.00%)  1
Metabolism and nutrition disorders     
Hypomagnesaemia  1  0/50 (0.00%)  0 3/50 (6.00%)  3
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  0/50 (0.00%)  0 3/50 (6.00%)  3
Nervous system disorders     
Headache  1  2/50 (4.00%)  3 5/50 (10.00%)  7
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Sponsor has no objection to publication of the results of the Study by Site based on information collected or generated by Site; provided, however, that such publication must not precede the primary manuscript (unless no such multi-site publication is completed within twelve (12) months following the completion of the Study or unless Sponsor notifies Site in writing that no such multi- center publication shall be made).
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Leslie Callahan
Organization: Veloxis Pharmaceutical
Phone: 732-321-3221
EMail: lca@veloxis.com
Layout table for additonal information
Responsible Party: Veloxis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01962922    
Other Study ID Numbers: LCP-Tacro 3004
First Submitted: October 8, 2013
First Posted: October 14, 2013
Results First Submitted: February 23, 2016
Results First Posted: August 15, 2016
Last Update Posted: June 6, 2018